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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 21
ISSUE: 28
DOI: 10.2174/0929867321666140601164647      Price:  $58









Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle

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Author(s): Vanessa Jacob Victorino, Luciana Pizzatti, Pamela Michelletti and Carolina Panis
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Pages 3211-3226 (16)
Abstract:
Chemotherapy continues to be the main treatment option for cancer. Although systemic chemotherapy can efficiently eradicate cancer cells, a significant proportion of patients carry tumors that present a chemoresistant phenotype, resulting in disease progression, cancer relapse, and reduced survival. It has also become clear that the effect of most chemotherapeutic drugs is associated with their capacity to generate reactive species (RS) that bind to specific structures within the cancer cell and promote cell death. Due to repeated exposure to chemotherapeutic agents, the redox homeostasis of cancer cells is continuously disturbed, which can result in changes to the cell’s ability to cope with excessive RS levels through the production of protective molecules. It is thought that the imbalance resulting from this process— oxidative stress—is toxic to cancer cells. Paradoxically, the metabolites produced during oxidative stress can favor the survival of some cancer subpopulations, which present specific gene signatures that confer a chemoresistant phenotype on these clones. Despite the huge amount of information generated by currently available technologies, we cannot predict whether this resistance will arise during chemotherapy and we still do not fully understand the mechanism by which it arises. In this review, we discuss the main findings regarding the role of oxidative stress signaling in cancer chemotherapy and the key redox molecules and pathways that lead to the development of chemoresistance.
Keywords:
Antineoplastic drugs, cancer, chemoresistance, chemotherapy, oxidative stress, redox homeostasis.
Affiliation:
Universidade Estadual do Oeste do Parana – UNIOESTE, Rua Maringa, 1200, Francisco Beltrao – PR, Brazil.